Review of Chemical Foundation

The Carbon Atom

Versatility of Carbon Bonding

Macromolecules Are the Major Constituents of Cells

Many biological molecules are macromolecules, polymers of high molecular weight assembled from relatively simple precursors.

Proteins, nucleic acids, and polysaccharides are produced by the polymerization of relatively small compounds with molecular weights of 500 or less. The number of polymerized units can range from tens to millions.

Synthesis of macromolecules is a major energy-consuming activity of cells.

Macromolecules themselves may be further assembled into supramolecular complexes, forming functional units such as ribosomes.

Three-Dimensional Structure Is Describedby Configuration and Conformation

Configuration refers to the order that is determined by chemical bonds. The configuration of a polymer cannot be altered unless chemical bonds are broken and reformed. Conformation refers to order that arises from the rotation of molecules about the single bonds. These two structures are studied below.

The covalent bonds and functional groups of a biomolecule are, of course, central to its function, but so also is the arrangement of the molecule’s constituent atoms in three-dimensional space—its stereochemistry.

A carbon-containing compound commonly exists as stereoisomers, molecules with the same chemical bonds but different stereochemistry—that is, different configuration, the fixed spatial arrangement of atoms.

Interactions between biomolecules are invariably stereospecific, requiring specific stereochemistry in the interacting molecules.

A carbon atom with four different substituents is said to be asymmetric, and asymmetric carbons are called chiral centers.

A molecule with only one chiral carbon can have two stereoisomers; when two or more (n) chiral carbons are present, there can be 2n stereoisomers.

Some stereoisomers are mirror images of each other; they are called enantiomers. Pairs of stereoisomers that are not mirror images of each other are called diastereomers.

Given the importance of stereochemistry in reactions between biomolecules, biochemists must name and represent the structure of each biomolecule so that its stereochemistry is unambiguous.

For compounds with more than one chiral center, the most useful system of nomenclature is the RS system.

In this system, each group attached to a chiral carbon is assigned a priority. The priorities of some common substituents are

For naming in the RS system, the chiral atom is viewed with the group of lowest priority pointing away from the viewer. If the priority of the other three groups (1 to 3) decreases in clockwise order, the configuration is (R) (Latin rectus, “right”); if in counterclockwise order, the configuration is (S) (Latin sinister, “left”).

In this way each chiral carbon is designated either (R) or (S), and the inclusion of these designations in the name of the compound provides an unambiguous description of the stereochemistry at each chiral center.

Plane-Polarized Light

• Ordinary light:Ordinary light: light vibrating in all planes perpendicular to its direction of propagation

• Plane-polarized light:Plane-polarized light: light vibrating only in parallel planes

• Optically active:Optically active: refers to a compound that rotates the plane of plane-polarized light

Plane-Polarized Light

– plane-polarized light is the vector sum of left and right circularly polarized light

– circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer

– the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization

Plane-Polarized Light

• Polarimeter:Polarimeter: a device for measuring the extent of rotation of plane-polarized light

Can You Make Your Own Polarimeter

?????

Specific Rotation• To have a basis for comparison, define

specific rotation, []D for an optically active compound

• []D = observed rotation/(pathlength x concentration)

= /(l x C) = degrees/(dm x g/mL)• Specific rotation is that observed for 1 g/mL in

solution in cell with a 10 cm path using light from sodium metal vapor (589 nanometers)

Optical Activity– observed rotation:observed rotation: the number of degrees, , through

which a compound rotates the plane of polarized light– dextrorotatory (+):dextrorotatory (+): refers to a compound that rotates

the plane of polarized light to the right– levorotatory (-):levorotatory (-): refers to a compound that rotates of

the plane of polarized light to the left– specific rotation:specific rotation: observed rotation when a pure

sample is placed in a tube 1.0 dm in length and concentration in g/mL (density); for a solution, concentration is expressed in g/ 100 mL

D-L System

3 Carbon Sugar ??

Used particularly often for naming sugars and aminoacids:

D-L System

D-L System

The simplest aldose, glyceraldehyde, contains one chiral center (the middle carbon atom) and therefore has two different optical isomers, or enantiomers.

By convention, one of these two forms is designated the D isomer, the other the L isomer.

As for other biomolecules with chiral centers, the absolutec configurations of sugars are known from x-ray crystallography.

To represent three-dimensional sugar structures on paper, we often use Fischer projection formulas.

The stereoisomers of monosaccharides of each carbon-chain length can be divided into two groups that differ in the configuration about the chiral center most distant from the carbonyl carbon.

Those in which the configuration at this reference carbon is the same as that of D glyceraldehyde are designated D isomers, and those with the same configuration as L glyceraldehyde are L isomers.

When the hydroxyl group on the reference carbon is on the right in the projection formula, the sugar is the D isomer; when on the left, it is the L isomer.

Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers.

• D,L designation refers to the configuration of the highest-

numbered asymmetric center.

• D,L only refers the stereocenter of interest back to D- and L-glyceraldehyde!

• D,L do not specify the sign of rotation of plane-polarized light!

• D-sugars predominate in nature.

The notation was extended to a-amino acids : L enantiomers are those in which the NH2 group is on the LHS of the Fischer projection in which the carboxyl group appears at the top.

Conversely, the D enantiomers are those in which the NH2 group is on the RHS. Thus (+)-alanine and (-)-serine are L-amino acids.

Distinct from configuration is molecular conformation, the spatial arrangement of substituent groups that, without breaking any bonds, are free to assume different positions in space because of the freedom of rotation about single bonds.

In the simple hydrocarbon ethane, for example, there is nearly complete freedom of rotation around the C-C bond.

Many different, interconvertible conformations of ethane are possible, depending on the degree of rotation.

Two conformations are of special interest: the staggered, which is more stable than all others and thus predominates, and the eclipsed, which is least stable.

We cannot isolate either of these conformational forms, because they are freely interconvertible.

However, when one or more of the hydrogen atoms on each carbon is replaced by a functional group that is either very large or electrically charged, freedom of rotation around the C-C bond is hindered.

This limits the number of stable conformations of the ethane derivative.

Interactions between Biomolecules Are Stereospecific

Biological interactions between molecules are stereospecific: the “fit” in such interactions must be stereochemically correct.

The three-dimensional structure of biomolecules large and small the combination of configuration and conformation—is of the utmost importance in their biological interactions: reactant with enzyme, hormone with its receptor on a cell surface, antigen with its specific antibody, for example.

The study of biomolecular stereochemistry with precise physical methods is an important part of modern research on cell structure and biochemical function.

In living organisms, chiral molecules are usually present in only one of their chiral forms.

For example, the amino acids in proteins occur only as their L isomers; glucose occurs only as its D isomer.

In contrast, when a compound with an asymmetric carbon atom is chemically synthesized in the laboratory, the reaction usually produces all possible chiral forms: a mixture of the D and L forms, for example. Living cells produce only one chiral form of biomolecules because the enzymes that synthesize them are also chiral.

Stereospecificity, the ability to distinguish between stereoisomers, is a property of enzymes and other proteins and a characteristic feature of the molecular logic of living cells.

If the binding site on a protein is complementary to one isomer of a chiral compound, it will not be complementary to the other isomer, for the same reason that a left glove does not fit a right hand.

Chirality in the Biological World– a schematic diagram of an enzyme surface

capable of binding with (R)-glyceraldehyde but not with (S)-glyceraldehyde

Physical Foundations of Biochemistry

Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings

The molecules and ions contained within a living organism differ in kind and in concentration from those in the organism’s surroundings.

A Paramecium in a pond, a shark in the ocean, an erythrocyte in the human bloodstream, an apple tree in an orchard—all are different in composition from their surroundings and,

Once they have reached maturity, all (to a first approximation) maintain a constant composition in the face of constantly changing surroundings.

Organisms Transform Energy and Matter from Their Surroundings

For chemical reactions occurring in solution, we can define a system as all the reactants and products present, the solvent that contains them, and the immediate atmosphere— in short, everything within a defined region of space.

The system and its surroundings together constitute the universe.

If the system exchanges neither matter nor energy with its surroundings, it is said to

be isolated.

If the system exchanges energy but not matter with its surroundings, it is a closed

system; if it exchanges both energy and matter with its surroundings, it is an open system.

living organism is an open system; it exchanges both matter and energy with its surroundings.

Living organisms derive energy from their surroundings in two ways: (1) they take up chemical fuels (such as glucose) from the environment and extract energy by oxidizing them; or (2) they absorb energy from sunlight

The first law of thermodynamics, developed from physics and chemistry but fully valid for biological systems as well, describes the principle of the conservation of energy:

in any physical or chemical change, the total amount of energy in the universe remains constant, although the form of the energy may change.

Cells are consummate transducers of energy, capable of interconverting chemical,

electromagnetic, mechanical, and osmotic energy with great efficiency

The Flow of Electrons Provides Energy for Organisms

Nearly all living organisms derive their energy, directly or indirectly, from the radiant energy of sunlight, which arises from thermonuclear fusion reactions carried out in the sun.

Photosynthetic cells absorb light energy and use it to drive electrons from water to carbon dioxide, forming energy-rich products such as glucose (C6H12O6), starch, and sucrose and releasing O2 into the atmosphere:

Creating and Maintaining Order Requires Work and Energy

DNA, RNA, and proteins are informational macromolecules.

In addition to using chemical energy to form the covalent bonds between the subunits in these polymers, the cell must invest energy to order the subunits in their correct sequence.

It is extremely improbable that amino acids in a mixture would spontaneously condense into a single type of protein, with a unique sequence.

This would represent increased order in a population of molecules; but according to the second law of thermodynamics, the tendency in nature is toward ever-greater disorder in the universe:

the total entropy of the universe is continually increasing.

To bring about the synthesis of macromolecules from their monomeric units, free energy must be supplied to the system (in this case, the cell).

The randomness or disorder of the components of a chemical system is expressed as entropy, S.

Any change in randomness of the system is expressed as entropy change, S, which by convention has a positive value when randomness increases.

J. Willard Gibbs, who developed the theory of energy changes during chemical reactions, showed that the free energy content, G, of any closed system can be defined in terms of three quantities: enthalpy, H, reflecting the number and kinds of bonds;entropy, S; and theabsolute temperature, T (in degrees Kelvin).

Gibbs free energy, G, expresses the amount of energy capable of doing work during a reaction at constant temperature and pressure. When a reaction proceeds with the release of free energy (that is, when the system changes so as to possess less free energy), the free-energy change, G, has a negative value and the reaction is said to be exergonic. In endergonic reactions, the system gains free energy and G is positive.

Examples of Entropy

Free Energy & SpontaneityWhat is the name of this molecule?

Free Energy & Spontaneity

Spontaneous Reaction Non-spontaneous Reaction

Source of Energy

Ene

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Cou

plin

g vi

a A

TP (1

/2)

Energy for Anabolism

The definition of free energy G

When a chemical reaction occurs at constant temperature, the free-energy change, G, is determined by the enthalpy change, H, reflecting the kinds and numbers of chemical bonds and noncovalent interactions broken and formed, and the entropy change, S, describing the change in the system’s randomness:

Enthalpy, H, is the heat content of the reacting system. It reflects the number and kinds of chemical bonds in the reactants and products.

When a chemical reaction releases heat, it is said to be exothermic; the heat content of the products is less than that of the reactants and H has, by convention, a negative value. Reacting systems that take up heat from their surroundings are endothermic and have positive values of H.

Entropy, S,

is a quantitative expression for the randomness or disorder in a system.

When the products of a reaction are less complex and more disordered than the reactants, the reaction is said to proceed with a gain in entropy.

The usual source of free energy in coupled biological reactions is the energy released by hydrolysis of phosphoanhydride bonds such as those in adenosine triphosphate.

At equilibrium G = 0.

K'eq, the ratio [C][D]/[A][B] at equilibrium, is the equilibrium constant.

An equilibrium constant (K'eq) greater than one indicates a spontaneous reaction (negative G').

G = Gº' + RT ln

= Gº' + RT ln

Gº' = - RTln

defining K'eq =

Gº' = - RT ln K'eq

[C] [D][A] [B]

[C] [D][A] [B]

[C] [D][A] [B]

[C] [D][A] [B]

When a reacting system is not at equilibrium, the tendency to move toward equilibrium represents a driving force, the magnitude of which can be expressed as the free-energy change for the reaction, G. Under standard conditions (298 K 25 C), when reactants and products are initially present at 1 M concentrations or, for gases, at partial pressures of 101.3 kilopascals (kPa), or 1 atm, the force driving the system toward equilibrium is defined as the standard free-energy change, G0.

By this definition, the standard state for reactions that involve hydrogen ions is [H] = 1 M, or pH 0.

Most biochemical reactions, however, occur in well-buffered aqueous solutions near pH 7; both the pH and the concentration of water (55.5 M) are essentially constant.

K'eqG º'

kJ/molStarting with 1 M reactants &products, the reaction:

104 - 23 proceeds forward (spontaneous)

102 - 11 proceeds forward (spontaneous)

100 = 1 0 is at equilibrium

10-2 + 11 reverses to form “reactants”

10-4 + 23 reverses to form “reactants”

Go' = RT ln K'eq

Variation of equilibrium constant with Go‘ (25 oC)

Free energy of oxidationof single-carbon compounds

In aerobic organisms, the ultimate electron acceptor in theoxidation of carbon is O2, and the oxidation product is CO2

The more reduced a carbon is, the more energy from its oxidation

One caution about the interpretation of G: thermodynamic constants such as this show where the final equilibrium for a reaction lies but tell us nothing about how fast that equilibrium will be achieved.

The rates of reactions are governed by the parameters of kinetics,

Tran

sitio

n S

tate

Che

mic

al R

eact

ion

Activa

tion E

nergy

ActivationEnergy

a.k.a., Substrateif enzyme catalyzed

Che

mic

al R

eact

ion

Note no change in degree of spontaneity, i.e., in G

Cat

alyz

ed R

eact

ion

At a given temperature catalyzed Rxns can run faster because less energy is required to achieve the transition state

Indu

ced

Fit (

Act

ive

Site

)

The Catalysis associated with Enzymes occurs within small regions on (or within)

proteins called Active Sites

Sub

tle A

pplic

atio

n of

Ene

rgy

Enz

yme

Cat

alyt

ic C

ycle

Input of ActivationEnergy

Mechanisms of CatalysisMetal Ion or =Organic Molecule

= OrganicCofactor

Polypeptide

Problem 1St Reaction of Glycolysis

Use the table to :1. Find standard transformed free energy change of this reaction2. Couple the reaction with ATP hydrolysis 3. Write the overall Reaction 4. Calculate the standard transformed free energy change of overall reaction

First Exam Next Monday

Let’s try to avoid the scholastic equivalent of this!